The Predictive Value of Genetic Analyses in the Diagnosis of Tetrahydrobiopterin (BH4)-Responsiveness in Chinese Phenylalanine Hydroxylase Deficiency Patients
Abstract Molecular characterization of PAH deficiency has been proven essential in establishing treatment options. We examine the diagnostic accuracy of two genetic assays to predict BH4 responsiveness: to determine whether the AV sum test or mutation-status assessment test can obviate the need for...
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Nature Portfolio
2017
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oai:doaj.org-article:271c1a010d6c442f91d35cccc51191022021-12-02T16:07:44ZThe Predictive Value of Genetic Analyses in the Diagnosis of Tetrahydrobiopterin (BH4)-Responsiveness in Chinese Phenylalanine Hydroxylase Deficiency Patients10.1038/s41598-017-06462-y2045-2322https://doaj.org/article/271c1a010d6c442f91d35cccc51191022017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06462-yhttps://doaj.org/toc/2045-2322Abstract Molecular characterization of PAH deficiency has been proven essential in establishing treatment options. We examine the diagnostic accuracy of two genetic assays to predict BH4 responsiveness: to determine whether the AV sum test or mutation-status assessment test can obviate the need for BH4 loading in Chinese patients. The overall predicted response in 346 patients was 31.65% by the AV sum test and 25.43% by the other assay; both percentages were lower than 51.06% derived from loading results in 94 patients. Responders were compound heterozygotes with definite BH4 responsive mutations, while non-responders had null/null ones; some consistently with specific mutations and genotypes. The sensitivity and specificity of the assays were 81.1% and 92.5% for the AV sum, and 82.9%, 97.3% for the other. An AV sum cutoff >2 has a positive predictive value (PPV) of 90.9%, while the presence of at least one BH4 responsive mutation has a PPV of 97.1%. The two approaches showed good concordance. Our data confirmed that the mutation-status assessment has a higher diagnostic accuracy in predicting response for Chinese patients than the AV sum test. BH4-responsiveness may be predicted or excluded from patients’ molecular characteristics to some extent, thus some patients may avoid the initial loading.Tianwen ZhuJun YeLianshu HanWenjuan QiuHuiwen ZhangLili LiangXuefan GuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017) |
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Medicine R Science Q Tianwen Zhu Jun Ye Lianshu Han Wenjuan Qiu Huiwen Zhang Lili Liang Xuefan Gu The Predictive Value of Genetic Analyses in the Diagnosis of Tetrahydrobiopterin (BH4)-Responsiveness in Chinese Phenylalanine Hydroxylase Deficiency Patients |
| description |
Abstract Molecular characterization of PAH deficiency has been proven essential in establishing treatment options. We examine the diagnostic accuracy of two genetic assays to predict BH4 responsiveness: to determine whether the AV sum test or mutation-status assessment test can obviate the need for BH4 loading in Chinese patients. The overall predicted response in 346 patients was 31.65% by the AV sum test and 25.43% by the other assay; both percentages were lower than 51.06% derived from loading results in 94 patients. Responders were compound heterozygotes with definite BH4 responsive mutations, while non-responders had null/null ones; some consistently with specific mutations and genotypes. The sensitivity and specificity of the assays were 81.1% and 92.5% for the AV sum, and 82.9%, 97.3% for the other. An AV sum cutoff >2 has a positive predictive value (PPV) of 90.9%, while the presence of at least one BH4 responsive mutation has a PPV of 97.1%. The two approaches showed good concordance. Our data confirmed that the mutation-status assessment has a higher diagnostic accuracy in predicting response for Chinese patients than the AV sum test. BH4-responsiveness may be predicted or excluded from patients’ molecular characteristics to some extent, thus some patients may avoid the initial loading. |
| format |
article |
| author |
Tianwen Zhu Jun Ye Lianshu Han Wenjuan Qiu Huiwen Zhang Lili Liang Xuefan Gu |
| author_facet |
Tianwen Zhu Jun Ye Lianshu Han Wenjuan Qiu Huiwen Zhang Lili Liang Xuefan Gu |
| author_sort |
Tianwen Zhu |
| title |
The Predictive Value of Genetic Analyses in the Diagnosis of Tetrahydrobiopterin (BH4)-Responsiveness in Chinese Phenylalanine Hydroxylase Deficiency Patients |
| title_short |
The Predictive Value of Genetic Analyses in the Diagnosis of Tetrahydrobiopterin (BH4)-Responsiveness in Chinese Phenylalanine Hydroxylase Deficiency Patients |
| title_full |
The Predictive Value of Genetic Analyses in the Diagnosis of Tetrahydrobiopterin (BH4)-Responsiveness in Chinese Phenylalanine Hydroxylase Deficiency Patients |
| title_fullStr |
The Predictive Value of Genetic Analyses in the Diagnosis of Tetrahydrobiopterin (BH4)-Responsiveness in Chinese Phenylalanine Hydroxylase Deficiency Patients |
| title_full_unstemmed |
The Predictive Value of Genetic Analyses in the Diagnosis of Tetrahydrobiopterin (BH4)-Responsiveness in Chinese Phenylalanine Hydroxylase Deficiency Patients |
| title_sort |
predictive value of genetic analyses in the diagnosis of tetrahydrobiopterin (bh4)-responsiveness in chinese phenylalanine hydroxylase deficiency patients |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/271c1a010d6c442f91d35cccc5119102 |
| work_keys_str_mv |
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1718384705369276416 |